Method and apparatus for treating wrinkles in skin using radiation

ABSTRACT

A method for treating wrinkles in skin involves the use of a beam of  puls scanned or gated continuous wave laser or incoherent radiation. The method comprises generating a beam of radiation, directing the beam of radiation to a targeted dermal region between 100 microns and 1.2 millimeters below a wrinkle in the skin, and thermally injuring collagen in the targeted dermal region. The beam of radiation has a wavelength of between 1.3 and 1.8 microns. The method may include cooling an area of the skin above the targeted dermal region while partially denaturing the collagen in the targeted dermal region. The method may also include cooling an area of the skin above the targeted dermal region prior to thermally injuring collagen in the targeted dermal region.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with Government support under Grant NumberN00014-94-1-0927 awarded by the Department of the Navy. The U.S.Government has certain rights in this invention.

FIELD OF THE INVENTION

The invention relates generally to the treatment of wrinkles in humanskin using radiation. In particular, the invention relates to a methodfor treating wrinkles in human skin using a beam of laser or incoherentradiation to cause thermal injury in the dermal region of the skinsufficient to elicit a healing response that produces substantiallyunwrinkled skin.

BACKGROUND OF THE INVENTION

Undesired wrinkles in skin are commonly seen in dermatologic practice.Wrinkles in skin may be caused by age and by exposure to the sun'sultraviolet rays. Human skin consists mainly of two layers: the toplayer of skin known as the epidermis; and the layer beneath theepidermis known as the dermis. The dermis is primarily acellular and iscomposed of water, the protein collagen, and glycosaminoglycans. Waterconstitutes approximately 70 percent of the total weight of the dermis.Collagen constitutes approximately 70 percent of the dry weight of thedermis, and glycosaminoglycans constitute between approximately 0.1 and0.3 percent of the dry weight of the dermis. Collagen andglycosaminoglycans are constantly produced by fibroblasts, a type ofconnective tissue cell, and degraded by enzymes. Collagen degradationrelies primarily on specific proteinases known as collagenases.

Collagen provides the dermis with the majority of its structuralintegrity. With aging, the amount of dermal collagen decreases and isreplaced by the protein elastin. In addition, the remaining collagentends to be chaotically oriented as compared to the more organizedpatterns found in youthful skin. Glycosaminoglycans are veryhydrophilic, and increased amounts of these carbohydrates are associatedwith the increased skin vigor found in youthful skin. One majordifference between the smooth, supple skin of newborns and the drier,thinned skin of older individuals is the far greater relative amount ofglycosaminoglycans found in newborn skin. The glycosaminoglycans foundin newborns can bind up to 1000 times their weight in water. As the skinages and the amount of glycosaminoglycans decreases, the skin may becomeless hydrated and lose some of the suppleness found in youth. Also, theremaining glycosaminoglycans in photo-aged skin are deposited on thehaphazardly arranged elastin fibers which have replaced the collagenfibers. The placement of the remaining glycosaminoglycans may partiallyaccount for the weather-beaten appearance of photo-aged skin.

Existing procedures for eliminating or reducing the severity of wrinklesinclude chemical peels, mechanical abrasion and laser ablation. All ofthese methods remove the top layer of skin. A new top layer forms duringhealing. Cosmetic improvement is seen when the skin containing wrinklesis replaced by a new layer of horizontally oriented neocollagen in thesuperficial dermis. However, all of these methods disrupt and completelyremove the epidermis. The resulting open wounds require daily care tooptimize wound healing. Epidermal destruction and subsequent healing hasseveral undesirable side effects. These undesirable side effects includeprolonged hypopigmentation, hyperpigmentation, erythema and edema.Hyperpigmentation occurs frequently in darker skin types as a result ofan inflammatory response of the skin. Hyperpigmentation results in thetreated area of the subject's skin turning darker than the surroundinguntreated skin. Hyperpigmentation can be slow to clear, sometimes takingup to a year to disappear. Hypopigmentation is attributable to damage tothe melanin-producing cells in the skin. While generally transient,hypopigmentation can be permanent, and is cosmetically undesirable whileit persists. Also, erythema or redness of the skin may be significantfor weeks to months after the procedure, requiring the patients to wearconspicuous amounts of make-up.

A known property of collagen fibers, such as those found in the skin, isthat the fibers shrink when elevated to a temperature in the range of 60to 70 degrees Celsius, which is about 30 degrees Celsius above normalbody temperature. Temperature elevation ruptures the collagenultrastructural stabilizing cross-links, and results in immediatecontraction in the collagen fibers to about one-third of their originallength without changing the structural integrity of the fibers. Oneknown technique shrinks the collagen fibers in the cornea of the eye tochange the shape of the cornea and correct refractive disorders. Thistechnique involves the use of laser energy in a wavelength range ofabout 1.80 to about 2.55 microns. The laser energy is used to irradiatethe collagen in the cornea to elevate the collagen to at least 23degrees Celsius above normal body temperature and thereby achievecollagen shrinkage. U.S. Pat. Nos. 4,976,709, 5,137,530, 5,304,169,5,374,265, and 5,484,432 to Sand disclose a technique and apparatus forcontrolled thermal shrinkage of collagen fibers in the cornea.

However, this technique cannot be effectively used to remove wrinkles inskin by shrinking dermal collagen. The bulk of the shrunken, thermallydenatured, collagen fibers do not remain in the skin after treatmentwith this technique. Unlike the cornea, which is avascular, anaggressive healing response in the skin degrades the denatured collagenin the superficial dermis by collagenases, thereby rapidly eliminatingthe bulk of the shrunken collagen from the skin.

Additionally, in the 1.80 to 2.55 micron wavelength range, strongabsorption of the laser energy by water present in the skin limits thepenetration depth of the laser radiation to a small fraction of amillimeter. The depths of thermal injury which can be achieved in skinusing the wavelengths in this range are therefore limited to the mostsuperficial layer of the skin. Such superficial injury leads to aninflammatory healing response characterized by prolonged visible edemaand erythema, as well as the possibility for long lasting pigmentarydisturbances.

SUMMARY OF THE INVENTION

The present invention addresses the foregoing problems and provides amethod for inducing remodeling of the skin's extracellular matrix bypartially denaturing the dermal collagen deeper in the skin, below thesurface, while avoiding injury to the epidermis and upper layers of thedermis. The invention offers numerous advantages over existingdermatologic procedures and devices. The surface of the skin remainsintact, thereby avoiding the need for dressing wounds; pigmentarydisturbances are minimized; and any inflammatory response to the injuryis mild and less visually evident.

In general, the present invention features a method for treatingwrinkles in skin, without removing a layer of skin, using a beam ofpulsed, scanned or gated continuous wave (CW) laser or incoherentradiation. The method comprises generating a beam of radiation having awavelength between 1.3 and 1.8 microns, directing the beam of radiationto a targeted dermal region between 100 microns and 1.2 millimetersbelow a wrinkle in the skin, and thermally injuring the targeted dermalregion to elicit a healing response that produces substantially lesswrinkles.

More specifically, causing selective thermal injury to the dermisactivates fibroblasts which deposit increased amounts of extracellularmatrix constituents (i.e., collagen and glycosaminoglycans). Theseincreases in extracellular matrix constituents are responsible fordermal skin rejuvenation and the reduced appearance of wrinkles.

In one embodiment, the beam of radiation causes partial denaturation ofthe collagen in the targeted dermal region. The partial denaturation ofthe collagen accelerates the collagen synthesis process by thefibroblasts and the deposition of new glycosaminoglycans, leading to theelimination or a reduction in the severity of the wrinkle. The methodmay also include cooling the surface of the skin and epidermal tissueabove the targeted dermal region while irradiating the skin. The methodmay also include cooling the surface of the skin prior to irradiatingthe skin.

In a detailed embodiment, the method also includes stretching the skinalong the wrinkle before directing the beam of radiation to the targeteddermal region below the wrinkle. Stretching the skin causes thermalinjury to the collagen fibers across the wrinkle, while not affectingthe fibers along the wrinkle.

The invention also relates to an apparatus for treating wrinkles inskin. The apparatus includes a radiation source and a delivery systemwhich includes a cooling system. The radiation source generates a beamof radiation having a wavelength between 1.3 and 1.8 microns. Thedelivery system directs the beam of radiation to a targeted dermalregion between 100 microns and 1.2 millimeters below a wrinkle in theskin. The cooling system cools the epidermal tissue above the targeteddermal region to minimize injury to the surface of the skin.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other objects, features and advantages of theinvention will become apparent from the following more particulardescription of preferred embodiments of the invention, as illustrated inthe accompanying drawings. The drawings are not necessarily to scale,emphasis instead being placed on illustrating the principles of thepresent invention.

FIG. 1 is an illustration of an apparatus including a radiation sourceand a delivery system for practicing the invention.

FIG. 2 is an enlarged perspective view of a delivery systemincorporating the principles of the invention.

FIG. 3 is an illustration of a wrinkle in skin exposed to a plurality ofradiation pulses.

FIG. 4 is an illustration of a region of skin exposed to a highlyconvergent beam of radiation.

DETAILED DESCRIPTION OF THE INVENTION

The present invention contemplates a system and method for removingwrinkles which includes delivering a beam of laser or incoherentradiation to cause sufficient thermal injury in the dermal region of theskin to elicit a healing response to cause the skin to remodel itself,resulting in more youthful looking (i.e., substantially unwrinkled)skin. In particular, thermal injury may be in the form of partialdenaturation of the collagen fibers in the targeted dermal region ofskin. In one embodiment, the radiation beam has a set of parameterranges carefully selected to partially denature collagen in the dermiswhile protecting the epidermis by surface cooling. As a result, asubject treated using the method of the invention is able to have theappearance of wrinkles lessened without damage to the epidermis.

FIG. 1 is an illustration of a system 10 for practicing the invention.The system 10 includes a radiation source 12 and a delivery system 13. Abeam of radiation generated by the radiation source 12 is directed to atarget region of a subject's skin including a wrinkle via the deliverysystem 13. In one embodiment, the radiation source 12 is a laser. Thelaser may generate a beam of pulsed, scanned or gated CW laserradiation. In another embodiment, the radiation source 12 generatesincoherent radiation.

The beam of radiation is directed to a targeted dermal region of skinbetween 100 microns and 1.2 millimeters below the wrinkle. The parameterranges for the beam have been specifically selected to cause thermalinjury to the dermis while avoiding injury to the epidermis and upperlayers of the dermis. In particular, the wavelength of the radiationbeam has been chosen to maximize absorption in the targeted region ofthe dermis, and the fluence or power density, depending on the type ofradiation, has been chosen to minimize erythema. The wavelength rangechosen has a tissue absorption coefficient preferably in the range ofabout 1 to 20 cm⁻¹. Thus, the beam preferably has a wavelength ofbetween about 1.3 and 1.8 microns in one embodiment. Within thiswavelength range, radiation energy applied through the surface of theskin is deposited predominantly in the dermal region of the skin. In oneembodiment, the radiation beam has a nominal wavelength of approximately1.5 microns. Lasers which produce radiation having wavelengths in therange of between about 1.3 and 1.8 microns include the 1.33 micronNd:YAG laser, the 1.44 micron Nd:YAG laser and the 1.54 micron Er:Glasslaser. The radiation beam may be pulsed, scanned or gated continuouswave laser radiation. In embodiments having a laser as the radiationsource 12, the laser radiation generated preferably has a fluence ofbetween about 10 and 150 joules.

In another embodiment, the radiation used to thermally injure the dermisis incoherent radiation. In embodiments using incoherent radiation, theincoherent radiation generated by the radiation source 12 preferably hasa power density of between about 5 and 100 watts per square centimeter.

FIG. 2 is an enlarged perspective view of a delivery system 13incorporating the principles of the invention. The delivery system 13includes a fiber 14 having a circular cross-section and a handpiece 16.A beam of radiation having a circular cross-section is delivered by thefiber 14 to the handpiece 16. An optical system within the handpiece 16projects an output beam of radiation to a targeted region of thesubject's skin. A user holding the handpiece 16 irradiates the targetedregion of the subject's skin including the wrinkle with output pulsesfrom the beam.

To minimize thermal injury to the epidermis and the upper layers of thedermis, in one embodiment, the delivery system 13 includes a coolingsystem for cooling the surface of the skin prior to and/or duringapplication of the radiation. In this embodiment, the delivery system 13is multi-functional and is capable of delivering radiation and coolingthe surface of the skin at the same time. FIG. 3 shows one embodiment ofa delivery system 13 which includes a cooling system. The handpiece 16includes a skin contacting portion 20 which is brought into contact withthe region of skin 22 receiving the beam of radiation 24. The skincontacting portion 20 cools the epidermal region of skin 22 receivingthe beam of radiation. The skin contacting portion 20 includes asapphire window 26 and a fluid passage 28 which contains a coolingfluid. The cooling fluid may be a fluorocarbon type cooling fluid. Thecooling fluid circulates through the fluid passage 28 and past thesapphire window 26 which is in contact with the epidermal region of skin22 receiving the beam of radiation 24.

In another embodiment, the delivery system 13 and the cooling system areseparate systems. The cooling system may comprise a container of a coldfluid. Cooling of the surface of the skin is accomplished by brieflyspraying the skin with the cold fluid which extracts heat from the skinon contact. The fluid used can also be a non-toxic substance with highvapor pressure at normal body temperature, such as a freon. These fluidsextract heat from the skin by the virtue of evaporative cooling.

FIG. 3 illustrates the treatment of a wrinkle 30 in accordance with theinvention. Radiation pulses are produced using the radiation source 12,which may be a pulsed, scanned or gated CW laser or incoherent radiationsource. The radiation pulses are directed toward the region 22 of thesubject's skin containing the wrinkle 30 by the delivery system 13. Theradiation pulses are preferably directed to a targeted dermal regionbetween 100 microns and 1.2 millimeters below the surface of the skin.In a detailed embodiment, the radiation pulses are focused to a regioncentered at a depth of about 750 microns. The targeted dermal regionincluding a portion of the wrinkle 30 is then irradiated with radiationpulses exiting from the handpiece 16 until collagen in that region ispartially denatured. To accomplish this, the collagen at the selecteddepth in the targeted dermal region is preferably heated to atemperature in the range of about 50 to 70 degrees Celsius. Partiallydenaturing collagen in the dermis accelerates the collagen synthesisprocess by the fibroblasts. The thermal injury caused by the radiationis mild and is only sufficient to elicit a healing response and causethe fibroblasts to produce new collagen. Excessive denaturation ofcollagen in the dermis causes prolonged edema, erythema, and potentiallyscarring.

The skin contacting portion 20 preferably cools the area of the skinabove the targeted dermal region to temperatures below approximately 50to 70 degrees Celsius during application of the radiation, so as not tocause collateral thermal damage to the epidermis. The radiation beam,due to its wavelength, does not sufficiently penetrate into depths belowthe targeted dermal region to cause thermal damage deeper in the skin.In one detailed embodiment, the skin contacting portion 20 cools an areaof the skin above the targeted dermal region before the radiation isapplied. The relative timing of cooling the surface of the skin toapplying radiation depends, in part, on the depth to which thermalinjury is to be prevented. Longer periods of cooling prior to theapplication of radiation allow more time for heat to diffuse out of theskin and cause a thicker layer of skin to be cooled, as compared to thethickness of the layer cooled by a short period of cooling. This thickerlayer of cooled tissue sustains less thermal injury when the radiationenergy is subsequently applied. Continued cooling of the surface of theskin during the delivery of radiation energy extracts heat from theupper layers of the skin as heat is deposited by the radiation, therebyfurther protecting the upper layers from thermal injury.

The depth of thermal injury caused by the radiation depends primarily onthe penetration depth of the radiation used. The penetration depth canbe approximated by taking the reciprocal of the absorption coefficientof the skin at the wavelength of the radiation. The thickness of thetissue overlying the zone of injury which is spared from injury dependsprimarily on the cooling applied prior to and/or during the delivery ofradiation energy. By suitably choosing the radiation wavelength, thetiming of the surface cooling, the cooling temperature, the radiationfluence and/or the power density as described above, the depth, thethickness and the degree of thermal injury can be confined to a zonewithin the dermis. These parameters can be chosen to optimally inducethe injury required to elicit remodeling within the dermis, whilesubstantially or completely sparing injury to the overlying epidermisand upper layers of the dermis.

In another detailed embodiment, the region of skin including the wrinkle30 is stretched along the wrinkle 30 before the beam of radiation isdirected to the targeted dermal region below the wrinkle 30. Stretchingthe skin along the wrinkle before irradiating the skin causes partialdenaturation of the collagen fibers across the wrinkle, while notdamaging the fibers along the wrinkle. Partially denaturing the fibersacross the wrinkle tightens the skin sufficiently to cause the wrinkleto disappear.

Referring to FIG. 4, in one embodiment, to counteract the effects ofscattering, the radiation beam is made highly convergent on the surfaceof the skin.

EXPERIMENTAL RESULTS

The method of the present invention for treating wrinkles in skin usingradiation was applied in a series of in vivo experiments performed onpigs. A pulsed erbium glass laser producing radiation having awavelength of approximately 1.54 microns was used as the radiationsource 12. The laser energy was applied to the pig skin via the skincontacting portion 20 equipped with a cooled sapphire window 26 at thetip, as described above and shown in FIGS. 1-3. The inner surface of thesapphire window 26 was cooled by circulating refrigerated coolant,chilled to approximately minus 25 degrees Celsius through the passage28. The coolant used was a halocarbon which is transparent to the 1.54micron laser radiation. The laser beam at the outer surface of thesapphire window 26 was approximately 5 mm in diameter.

The tip of the skin contacting portion 20 was placed in contact with theskin to cool the skin prior to applying the laser radiation. After a setamount of time (hereinafter "the pre-cooling time"), laser energy wasapplied to the skin. Various combinations of pre-cooling times, laserpulse energies, laser pulse repetition frequencies, time intervals oflaser energy delivery, and total number of laser pulses delivered werestudied. It was found that by the appropriate choice of theseparameters, varying degrees of thermal injury can be achieved at varyingdepths in the dermis while preserving the viability of the epidermis andupper dermis.

For example, using a pre-cooling time of 5 seconds, a laser energy inthe range of between 0.2 and 0.8 joules per pulse at a pulse repetitionfrequency of 4 Hertz (corresponding to an average laser power in therange between 0.8 to 3.2 watts), and a total of 24 pulses, it was foundthat varying degrees of thermal injury could be induced in a zonecentered at a depth in the range of approximately 0.5 to 1.0 millimetersbeneath the surface of the skin, while avoiding injury to the epidermisand upper dermis.

Histology performed on biopsy samples taken at sites treated with theabove range of parameters revealed collagen denaturation extending fromabout 100 microns in the dermis to about 1 mm deep. The epidermis andupper layers of the dermis were preserved as confirmed withnitrotetrazolium blue, a viability stain. In the cases in which onlypartial collagen denaturation was shown on histology, clinically, thetreated areas showed an intact epidermis with mild edema and erythemawhich resolved completely within two weeks. Histologically, the treatedsites showed greatly increased fibroblast activity, new collagensecretion and degradation of denatured collagen. By four weeks posttreatment, the treated sites returned to normal, both clinically andhistologically.

EQUIVALENTS

While the invention has been particularly shown and described withreference to specific embodiments, it should be understood by thoseskilled in the art that various changes in form and detail may be madetherein without departing from the spirit and scope of the invention asdefined by the appended claims.

What is claimed is:
 1. A method for treating a wrinkle in human skin,comprising:generating a beam of radiation having a wavelength of between1.3 and 1.8 microns and a fluence of between 10 and 150 joules persquare centimeter; directing the beam of radiation to a targeted dermalregion between 100 microns and 1.2 millimeters below a wrinkle in theskin; and causing thermal injury within the targeted dermal region toelicit a healing response that produces substantially unwrinkled skin.2. The method of claim 1 wherein the wavelength is about 1.5 microns. 3.The method of claim 1 further comprising the step of stretching the skinalong the wrinkle before the step of directing the beam of radiation tothe targeted dermal region.
 4. The method of claim 1 further comprisingthe step of cooling an epidermal region of the skin above the targeteddermal region contemporaneously with the step of causing thermal injurywithin the targeted dermal region.
 5. The method of claim 4 furthercomprising the step of pre-cooling the epidermal region of the skinabove the targeted dermal region before the step of causing thermalinjury within the targeted dermal region.
 6. A method for treating awrinkle in human skin, comprising:generating a beam of radiation havinga wavelength of between 1.3 and 1.8 microns and a power density ofbetween 5 and 100 watts per square centimeter; directing the beam ofradiation to a targeted dermal region between 100 microns and 1.2millimeters below a wrinkle in the skin; and causing thermal injurywithin the targeted dermal region to elicit a healing response thatproduces substantially unwrinkled skin.
 7. The method of claim 6 whereinthe wavelength is about 1.5 microns.
 8. The method of claim 6 furthercomprising the step of stretching the skin along the wrinkle before thestep of directing the beam of radiation to the targeted dermal region.9. The method of claim 6 further comprising the step of cooling anepidermal region of the skin above the targeted dermal regioncontemporaneously with the step of causing thermal injury within thetargeted dermal region.
 10. The method of claim 9 further comprising thestep of pre-cooling the epidermal region of the skin above the targeteddermal region before the step of causing thermal injury within thetargeted dermal region.
 11. An apparatus for treating a wrinkle in humanskin, comprising:a source generating a beam of radiation having awavelength of between 1.3 and 1.8 microns; and a delivery system coupledto the source, wherein the delivery system is for directing the beam ofradiation to a targeted dermal region between 100 microns and 1.2millimeters below a wrinkle in the skin, wherein the beam of radiationcauses thermal injury to the targeted dermal region sufficient to elicita healing response that produces substantially unwrinkled skin, thedelivery system further comprising:a cooling system for contact coolingan epidermal region of the skin above the targeted dermal region, tothereby minimize injury to the epidermal region.
 12. The apparatus ofclaim 11 wherein the delivery system further comprises a fiber coupledto the source, the fiber carrying the beam of radiation; andwherein thecooling system further comprises a skin contacting portion having afirst end in optical communication with the fiber and a second end, theskin contacting portion projecting the beam of radiation toward thetargeted dermal region through the second end of the skin contactingportion.
 13. The apparatus of claim 12 wherein the skin contactingportion further comprises a window located at the second end of the skincontacting portion, the window being in optical communication with thefiber; andwherein the skin contacting portion has a fluid passageextending across at least a portion of the window, the fluid passagecirculating a cooling fluid past the window.
 14. An apparatus fortreating a wrinkle in human skin, comprising:a source generating a beamof radiation having a wavelength of between 1.3 and 1.8 microns; adelivery system coupled to the source, wherein the delivery system isfor directing the beam of radiation to a targeted dermal region between100 microns and 1.2 millimeters, below a wrinkle in the skin, whereinthe beam of radiation causes thermal injury to the targeted dermalregion sufficient to elicit a healing response that producessubstantially unwrinkled skin; and a cooling system for cooling anepidermal region of the skin above the targeted dermal region, tothereby minimize injury to the epidermal region.
 15. The apparatus ofclaim 14 wherein the cooling system comprises a container of cold fluid,wherein the cold fluid can be sprayed onto the skin to extract heat fromthe skin on contact.